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Pathogenesis and mechanisms of protease antigen-induced innate-type airway inflammation

Research Project

Project/Area Number 23390262
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

MATSUMOTO Kenji  独立行政法人国立成育医療研究センター, その他部局等, その他 (60181765)

Co-Investigator(Kenkyū-buntansha) SAITO Hirohisa  独立行政法人国立成育医療研究センター, 研究所免疫アレルギー研究部, 副所長 (40130166)
NAKAE Susumu  東京大学医科学研究所システム疾患モデル研究センター, システムズバイオロジー研究分野, 准教授 (60450409)
OOBOKI Keisuke  独立行政法人国立成育医療研究センター, 研究所免疫アレルギー研究部, 上級研究員 (80415108)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsIL-33 / プロテアーゼ / アレルギー・ぜんそく / アレルギー / 喘息 / サイトカイン / アレルゲン
Research Abstract

After inhalation of papain (mimic of allergen with protease activity), we found 1. Early reaction (1 day) with neutrophil-dominant inflammation was induced by IL-33-release via activation of non-T cells, whereas late reaction (7 days) with eosinophil-dominant inflammation was induced by IL-33-release via activation of rag-2+ cells. 2. Biphasic (6h and 72 h) IL-13 induction was observed after IL-33 release which peaks at 6h after inhalation. 3. Immune response against papain varied with gender, age and strain. These findings may help understanding the development and pathogenesis of bronchial asthma.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report

Research Products

(29 results)

All 2014 2013 2012 2011

All Journal Article

  • [Journal Article] Silica and double-stranded RNA synergistically induce bronchial epithelial apoptosis and airway inflammation.2014

    • Author(s)
      Unno H, Futamura K, Morita H, Kojima R, Arae K, Nakae S, Ida H, Saito H, Matsumoto K, Matsuda A
    • Journal Title

      Am J Respir Cell Mol Biol.

      Volume: (in press) Pages: 344-353

    • DOI
      10.1165/rcmb.2013-0281oc
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line.2014

    • Author(s)
      Kojima R, Ohno T, Iikura M, Niki T, Hirashima M, Iwaya K, Tsuda H, Nonoyama S, Matsuda A, Saito H, Matsumoto K, Nakae S
    • Journal Title

      PLoS One.

      Volume: 9

    • DOI
      10.1371/journal.pone.0086106
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] GATA-1 regulates the generation and function of basophils.2014

    • Author(s)
      Nei Y, Obata-Ninomiya K, Tsutsui H, Ishiwata K, Miyasaka M, Matsumoto K, Nakae S, Kanuka H, Inase N, Karasuyama H
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 110 Pages: 18620-18625

    • DOI
      10.1073/pnas.1311668110
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-33, but not IL-25, is crucial for the development of house dust mite antigen-induced allergic rhinitis.2014

    • Author(s)
      Nakanishi W, Yamaguchi S, Matsuda A, Suzukawa M, Shibui A, Nambu A, Kondo K, Suto H, Saito H, Matsumoto K, Yamasoba T, Nakae S
    • Journal Title

      PLoS One.

      Volume: 8

    • DOI
      10.1371/journal.pone.0078099
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Silica and Double-Stranded RNA Synergistically Induce Bronchial Epithelial Apoptosis and Airway Inflammation.2014

    • Author(s)
      Unno H, Futamura K, Morita H, Kojima R, Arae K, Nakae S, Ida H, Saito H, Matsumoto K, Matsuda A.
    • Journal Title

      Am J Respir Cell Mol Biol.

      Volume: In press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] [Role of IL-25 and IL-33 in allergic diseases].2014

    • Author(s)
      Morita H, Unno H, Arae K, Ohno T, Saito H, Matsumoto K, Nakae S.
    • Journal Title

      Arerugi

      Volume: 62 Pages: 924-935

    • NAID
      110009649375
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Interleukin-33 in Innate-Type Immune Cells in Allergy2013

    • Author(s)
      Nakae S, Morita H, Ohno T, Arae K, Matsumoto K, Saito H
    • Journal Title

      Allergol. Int.

      Volume: 62 Issue: 1 Pages: 13-20

    • DOI
      10.2332/allergolint.13-RAI-0538
    • NAID
      130004477181
    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of IL-25 and IL-33 in allergic diseases2013

    • Author(s)
      Morita H, Unno H, Arae K, Ohno T, Saito H, Matsumoto K, Nakae S
    • Journal Title

      Arerugi

      Volume: 62 Pages: 924-35

    • NAID
      110009649375
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salivary cortisol response to stress in young children with atopic dermatitis2013

    • Author(s)
      Kojima R, Matsuda A, Nomura I, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K.
    • Journal Title

      Pediatr Dermatol

      Volume: 30 Pages: 17-22

    • DOI
      10.1111/j.1525-1470.2012.01770.x
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors associated with steroid phobia in caregivers of children with atopic dermatitis2013

    • Author(s)
      Kojima R, Fujiwara T, Matsuda A, Narita M, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K.
    • Journal Title

      Pediatr Dermatol

      Volume: 30 Pages: 29-35

    • DOI
      10.1111/j.1525-1470.2012.01808.x
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of human synovial mast cells from rheumatoid arthritis or osteoarthritis patients in response to aggregated IgG through FcgammaRI and FcgammaRII.2013

    • Author(s)
      Lee H, Kashiwakura J, Matsuda A, Watanabe Y, Sakamoto-Sasaki T, Matsumoto K, Hashimoto N, Saito S, Ohmori K, Nagaoka M, Tokuhashi Y, Ra C, Okayama Y.
    • Journal Title

      Arthritis Rheum

      Volume: 65(1) Pages: 109-119

    • DOI
      10.1002/art.37741
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of diesel exhaust particles on primary cultured healthy human conjunctivalツepithelium.2013

    • Author(s)
      Fujishima H, Satake Y, Okada N, Kawashima S, Matsumoto K, Saito H.
    • Journal Title

      Ann Allergy Asthma Immunol.

      Volume: 110 Pages: 39-43

    • DOI
      10.1016/j.anai.2012.10.017
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH22013

    • Author(s)
      Morita H, Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M, Shoda T, Matsuda A, Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 131 Pages: 590-2

    • DOI
      10.1016/j.jaci.2012.09.005
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma2012

    • Author(s)
      Suzukawa M, Morita H, Nambu A, Arae K,Shimura E, Shibui A, Yamaguchi S, Suzukawa K, Nakanishi W, Oboki K, Kajiwara N, Ohno T, Ishii A, Korner H, Cua DJ, Suto H,Yoshimoto T, Iwakura Y, Yamasoba T, Ohta K, Sudo K, Saito H, Okumura K, Broide DH,Matsumoto K, Nakae S.
    • Journal Title

      Journal of Immunology

      Volume: 189(7) Pages: 3641-52

    • DOI
      10.4049/jimmunol.1200461
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy2012

    • Author(s)
      Kashiwakura JC, Ando T, Matsumoto K, Kimura M, Kitaura J, Matho MH, Zajonc DM, Ozeki T, Ra C, MacDonald SM, Siraganian RP, Broide DH, Kawakami Y, Kawakami T
    • Journal Title

      J Clin Invest

      Volume: 122 Pages: 218-228

    • DOI
      10.1172/jci59072
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The alarmin interleukin-33 drives protective antiviral CD8^+T cell responses2012

    • Author(s)
      Bonilla WV, Fröhlich A, Senn K, Kallert S, Fernandez M, Johnson S, Kreutzfeldt M, Hegazy AN, Schrick C, Fallon PG, Klemenz R, Nakae S, Adler H, Merkler D, Löhning M, Pinschewer DD
    • Journal Title

      Science

      Volume: 335(6071) Pages: 984-9

    • DOI
      10.1126/science.1215418
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness.2012

    • Author(s)
      Sawaguchi, M.
    • Journal Title

      J. Immunol.

      Volume: 188 Pages: 1809-18

    • DOI
      10.4049/jimmunol.1101746
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ST2 Requires Th2-, but Not Th17-, Type Airway Inflammation in Epicutaneously Antigen-Sensitized Mice2012

    • Author(s)
      Morita H, Arae K, Ohno T, Kajiwara N, Oboki, K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Matsumoto K, Nakae, S
    • Journal Title

      Allergol. Int.

      Volume: 61(2) Issue: 2 Pages: 265-273

    • DOI
      10.2332/allergolint.11-OA-0379
    • NAID
      130004477129
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory effects of high-dose IgG on TNF-alpha-activated human coronary artery endothelial cells2012

    • Author(s)
      Matsuda A, Morita H, Unno H, Saito H, Matsumoto K, Hirao Y, Munechika K, Abe J
    • Journal Title

      Eur J Immunol

      Volume: 42 Pages: 2121-2131

    • DOI
      10.1002/eji.201242398
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-IgE-mediated gastrointestinal food allergies: distinct differences in clinical phenotype between Western countries and Japan.2012

    • Author(s)
      Nomura I, Morita H, Ohya Y, Saito H, Matsumoto K.
    • Journal Title

      Curr Allergy Asthma Rep.

      Volume: 12 Pages: 297-303

    • DOI
      10.1007/s11882-012-0272-5
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma.2012

    • Author(s)
      Suzukawa M, Morita H, Nambu A, Matsumoto K, et al.
    • Journal Title

      J Immunol.

      Volume: 189 Pages: 3641-52

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-33 in allergy2012

    • Author(s)
      Ohno T, Morita H, Arae K, Matsumoto K, Nakae S.
    • Journal Title

      Allergy

      Volume: 67 Pages: 1203-1214

    • DOI
      10.1111/all.12004
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of Staphylococcal enterotoxin in atopic keratoconjunctivitis and corneal ulceration.2012

    • Author(s)
      Fujishima H, Okada N, Dogru M, Baba F, Tomita M, Abe J, Matsumoto K, Saito H.
    • Journal Title

      Allergy.

      Volume: 67 Pages: 799-803

    • DOI
      10.1111/j.1398-9995.2012.02818.x
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paracrine IL-33 enhances lipoplysaccharide-mediated macrophage activation2011

    • Author(s)
      Ohno T., Oboki K., Kajiwara N., Tanaka S., Ikeda M., Iikura M., Akiyama T., Inoue J., Matsumoto K., Sudo K., Azuma M.,
    • Journal Title

      PLoS ONE

      Volume: 6 Pages: 18404-18404

    • DOI
      10.1371/journal.pone.0018404
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-33 and airway inflammation2011

    • Author(s)
      Oboki, K, Nakae, S, Matsumoto K, Saito, H
    • Journal Title

      Allergy, Asthma & Immunology Research

      Volume: 3(2) Pages: 81-8

    • DOI
      10.4168/aair.2011.3.2.81
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations2011

    • Author(s)
      Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K
    • Journal Title

      PLoS Genetics

      Volume: 7(7) Pages: 1002170-1002170

    • DOI
      10.1371/journal.pgen.1002170
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral blood mononuclear cells from patients with bronchial asthma show impaired innate immune responses to rhinovirus in vitro2011

    • Author(s)
      Iikura K, Katsunuma T, Saika S, Saito S, Ichinohe S, Ida H, Saito H, Matsumoto K
    • Journal Title

      Int Arch Allergy Immunol

      Volume: 155 Pages: 27-33

    • DOI
      10.1159/000327262
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Journal Article] Cimetidine Enhances Antigen-Specific IgE and Th2 Cytokine Production2011

    • Author(s)
      Arae K, Oboki, K, Ohno T, Hirata M, Nakae, S, Taguchi H, Saito, H, Nakajima T
    • Journal Title

      Allergol. Int.

      Volume: 60(3) Issue: 3 Pages: 339-344

    • DOI
      10.2332/allergolint.10-OA-0255
    • NAID
      130004723046
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eosinophilic gastrointestinal disorders in infants: a Japanese case series.2011

    • Author(s)
      Yamada Y, et al
    • Journal Title

      Int Arch Allergy Immunol.

      Volume: 155Suppl1 Pages: 40-45

    • DOI
      10.1159/000327264
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed

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Published: 2011-04-06   Modified: 2019-07-29  

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